Match!

Pathologies liées aux déficits du cycle de Krebs

Published on Apr 1, 2018in Revue Francophone Des Laboratoires
· DOI :10.1016/s1773-035x(18)30120-5
Paule Bénit29
Estimated H-index: 29
(French Institute of Health and Medical Research),
Sylvie Bortoli8
Estimated H-index: 8
(Paris V: Paris Descartes University)
+ 2 AuthorsPierre Rustin80
Estimated H-index: 80
(French Institute of Health and Medical Research)
Abstract
Resume Chez l'homme, les dysfonctions des enzymes du cycle de Krebs liees a des mutations causent des encephalopathies severes du jeune enfant, ou differents types de tumeurs et de cancers touchant differents organes. Ainsi des mutations des genes de la succinate-deshydrogenase ont ete identifiees dans des formes familiales de pheochromocytomes et paragangliomes. Les mutations du gene de la fumarase s'observent dans des leiomyomes uterins en association avec des cancers renaux, mais des cas d'encephalopathies de l'enfant ont aussi ete observes. Les mutations des genes de l'isocitrate-deshydrogenase peuvent representer jusqu'a 20% des leucemies myeloides aigues et jusqu'a 80% dans certains gliomes. On ne sait actuellement expliciter la diversite des consequences possibles de ces mutations : encephalopathies versus cancers, nature des tissus affectes, cinetique variable d'apparition des symptomes. Il semble en revanche etabli que les anomalies dans les equilibres metaboliques qui resultent de ces mutations soient a la base des processus tumoraux en modulant l'activite d'hydroxylases susceptibles d'affecter certains facteurs de transcriptions, mais aussi la methylation de l'ADN et les histones. Dans ce contexte, il semble etonnant que soient largement utilises certains fongicides dont l'effet est de bloquer une etape centrale du cycle de Krebs, la succinate-deshydrogenase. Le principe de precaution voudrait sans aucun doute de reevaluer urgemment la necessite de l'usage de telles substances pour l'homme et l'environnement.
  • References (28)
  • Citations (0)
References28
Newest
#1Masao Yamashita (Rothamsted Research)H-Index: 1
#2Bart A. Fraaije (Rothamsted Research)H-Index: 30
BACKGROUND A new generation of more active succinate dehydrogenase (Sdh) inhibitors (SDHIs) is currently widely used to control Septoria leaf blotch in northwest Europe. Detailed studies were conducted on Zymoseptoria tritici field isolates with reduced sensitivity to fluopyram and isofetamid; SDHIs which have only just or not been introduced for cereal disease control, respectively. RESULTS Strong cross‐resistance between fluopyram and isofetamid, but not with other SDHIs, was confirmed through...
9 CitationsSource
#1Caspar A. Hallmann (Radboud University Nijmegen)H-Index: 7
#2Martin SorgH-Index: 1
Last. Hans de Kroon (Radboud University Nijmegen)H-Index: 46
view all 12 authors...
Global declines in insects have sparked wide interest among scientists, politicians, and the general public. Loss of insect diversity and abundance is expected to provoke cascading effects on food webs and to jeopardize ecosystem services. Our understanding of the extent and underlying causes of this decline is based on the abundance of single species or taxonomic groups only, rather than changes in insect biomass which is more relevant for ecological functioning. Here, we used a standardized pr...
388 CitationsSource
#1Dylan G. Ryan (Trinity College, Dublin)H-Index: 7
#2Luke A. J. O'Neill (Trinity College, Dublin)H-Index: 106
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, ...
25 CitationsSource
#1Karishma Sajnani (Griffith University)H-Index: 1
#2Farhadul Islam (Griffith University)H-Index: 12
Last. Alfred King-Yin Lam (Griffith University)H-Index: 35
view all 5 authors...
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydr...
17 CitationsSource
#1Douglass M. Turnbull (Newcastle University)H-Index: 93
#2Pierre Rustin (French Institute of Health and Medical Research)H-Index: 80
Abstract The major progress made in the identification of the molecular bases of mitochondrial disease has revealed the huge diversity of their origin. Today up to 300 mutations were identified in the mitochondrial genome and about 200 nuclear genes are possibly mutated. In this review, we highlight a number of features specific to mitochondria which possibly participate in the complexity of these diseases. These features include both the complexity of mitochondrial genetics and the multiplicity...
17 CitationsSource
#1Antonio Abad Fuentes (CSIC: Spanish National Research Council)H-Index: 17
#2Eric Ceballos-Alcantarilla (University of Valencia)H-Index: 3
Last. Francesc A. Esteve Turrillas (CSIC: Spanish National Research Council)H-Index: 19
view all 6 authors...
In recent years, a second generation of succinate-dehydrogenase-inhibitor (SDHI) fungicides has been introduced into the market for effective treatment of fruit and vegetable crops, with fluxapyroxad, boscalid, fluopyram, penflufen, bixafen, penthiopyrad, and isopyrazam being some of the members of this new class of agrochemical. We herein report the development of an analytical procedure for the determination of residues of these SDHI fungicides in food samples, based on a modification of the Q...
22 CitationsSource
#1Bryce W. CareyH-Index: 12
#2Lydia W. S. FinleyH-Index: 21
Last. Craig B. ThompsonH-Index: 166
view all 5 authors...
If deprived of exogenous glutamine, naive mouse embryonic stem cells are shown to be capable of generating the amino acid from other sources to enable their proliferation; the stem cells use glutamine and glucose catabolism to maintain a high level of intracellular α-ketoglutarate and promote demethylation of chromatin and ensure sufficient expression of pluripotency-associated genes.
332 CitationsSource
#1Aurélie Morin (Paris V: Paris Descartes University)H-Index: 12
#2Eric LetouzéH-Index: 24
Last. Judith Favier (Paris V: Paris Descartes University)H-Index: 35
view all 4 authors...
Although the alteration of cellular metabolism in cancer was reported by Warburg in the early 1930s, a regain of interest in cancer metabolism has more recently followed the discovery of germline or somatic mutations in genes coding for metabolic enzymes (succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase) that are associated with tumor susceptibility. Mutations in these genes are found in numerous tumor types including paragangliomas, kidney cancers, leiomyomas, glioblasto...
65 CitationsSource
#1Paule Bénit (French Institute of Health and Medical Research)H-Index: 29
#2Eric LetouzéH-Index: 24
Last. Pierre Rustin (French Institute of Health and Medical Research)H-Index: 80
view all 8 authors...
Abstract Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonethel...
26 CitationsSource
#1Shaobai Huang (UWA: University of Western Australia)H-Index: 23
#2A. Harvey Millar (UWA: University of Western Australia)H-Index: 75
Succinate dehydrogenase (SDH) oxidises succinate to fumarate as a component of the tricarboxylic acid cycle and ubiquinone to ubiquinol in the mitochondrial electron transport chain. Studies of SDH mutants have revealed far-reaching effects of altering succinate oxidation in plant cells. The plant SDH complex composition, structure and assembly are all beginning to be understood but the implications of the divergence across eukaryotes is still unclear. We propose an integration of the reported p...
50 CitationsSource
Cited By0
Newest
#1Paule Bénit (University of Paris)H-Index: 16
#2Agathe Kahn (University of Paris)H-Index: 1
Last. Pierre Rustin (University of Paris)H-Index: 80
view all 11 authors...
Succinate dehydrogenase (SDH) inhibitors (SDHIs) are used worldwide to limit the proliferation of molds on plants and plant products. However, as SDH, also known as respiratory chain (RC) complex II, is a universal component of mitochondria from living organisms, highly conserved through evolution, the specificity of these inhibitors toward fungi warrants investigation. We first establish that the human, honeybee, earthworm and fungal SDHs are all sensitive to the eight SDHIs tested, albeit with...
1 CitationsSource